Breast cancer is the most common cancer in women in the world. As the pathogenesis of breast cancer is inadequately understood, the early diagnosis seemed much of significance. Currently, mammogram screening is the most frequent method for the breast cancer detection. It can be used to reduce breast cancer morbidity by 20 to 40 percent in the age of 40 to 69 women, which has been proved by several large randomized trials. Mammography is currently the gold standard for early breast cancer detection while the reported overall sensitivity is significantly reduced in certain subsets of women, particularly in women with radiographically dense breasts and those at increased risk of breast cancer. Estimates of film mammographic sensitivity in women with extremely dense breasts range from 48 to 63%. Mammography has the disadvantage of low sensitivity and specificity, especially in the young group, and a compression pain during the process. In addition, due to small volume and high-density breast, many cases failed to obtain a clear result of their mammography in the screening, which are often classified as BI-RADS 0 (BI-RADS: Breast Imaging Reporting and Data System) in their mammographic diagnosis.
The BI-RADS was developed in 1993 by the American College of Radiology (ACR) to standardize mammographic reporting, to improve communication, to reduce confusion regarding mammographic findings, to aid research, and to facilitate outcomes monitoring. According to the Mammography Quality Standards Act (MQSA) of 1997 [Final Rule 62(208):55988], all mammograms in the United States must be reported using one of these assessment categories. Each mammographic study should be assigned a single assessment based on the most concerning findings. Classifications are divided into an incomplete assessment (category 0) and completed assessments (categories 1, 2, 3, 4, 5, 6). BI-RADS Category 0 is defined as an incomplete assessment, which means additional imaging needed. Follow-up is usually recommended, which requires a long, expensive and anxiety producing process, based on ultrasonography or magnetic resonance imaging (MRI) or even biopsy. Ultrasonography, even combined with mammography, is associated with high rate of false positive results which led to unnecessary invasive steps. The long term of reservation of MRI is detrimental to the patients. MRI also brings a high rate of false positive result, together with a high cost. With such a variety of factors, the need of a new easy-to go test that would improve breast cancer detection and demonstrate the risk of patients, particularly when mammography cannot be identified, is highly important.
The serum biomarker, such as CEA, CA15-3, does not show a good performance in the cancer screening [1]. Recently, there is some literature describe the possibility of early diagnosis of breast cancer using gene-expression patterns in peripheral blood cells [2]. The result of these pilot studies indicate that cancer would cause characteristic changes in the biochemical environment of blood, and as a result of that the expression pattern of some identified genes can be used to discriminate cancer and control group with high accuracy. However, no alternative based on blood biomarkers has yet succeeded to discriminate within the BI-RADS 0 patients, between breast cancer (BC) and benign breast disease (BBD).